Mesdopetam (IRL790) is an experimental small molecule compound with psychomotor stabilizing properties. The primary target is the dopamine D3 receptor, a target implicated in the generation of levodopa-induced dyskinesia, a side-effect frequently occurring with long-term levodopa treatment in patients with Parkinson's disease. In experimental animals mesdopetam potently reduced levodopa-induced involuntary movement without impairing the antiparkinsonian effect of levodopa. The primary purpose of the trial is to investigate whether mesdopetam given as adjunctive treatment can reduce levodopa induced dyskinesia in patients with Parkinson's disease. The trial will also help to establish the most optimal dosing of the compound.
METHODOLOGY: This is a multicentre study where 74 patients with Parkinson's disease exhibiting levodopa induced dyskinesia will be randomised to receive study drug or placebo. Thirty seven patients will be randomised to mesdopetam and 37 patients to placebo (1:1 randomisation). Patients will be screened for eligibility according to inclusion/exclusion criteria within four weeks of initiation of study treatment (Screening visit). An outpatient study with the patients taking the study drug for four weeks at home. Mesdopetam will be taken twice daily (b.i.d.) as adjunctive treatment to the patients' regular and stable antiparkinsonian medication. The first two weeks of treatment will allow for per patient titration of study medication to the highest tolerated predefined dose, after which patients will continue on this highest tolerated dose for an additional two weeks. Changes in disease state and dyskinesia will be measured using the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Unified Dyskinesia Rating Scale (UDysRS); furthermore, patients will administer two 24-hour diaries on run-in and on the fourth week of dosing to assess daily movements. Pharmacokinetic (PK) samples will be collected for the determination of concentrations of mesdopetam and its metabolites IRL902 and IRL872 in plasma. They will be collected before and after IMP administration at two visits. A Follow-up Visit will be performed for all patients five to eight days after last administration of IMP.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
75
Mesdopetam (IRL790) capsule
Sahlgrenska University hospital
Gothenburg, Sweden
University hospital
Linköping, Sweden
University hospital
Lund, Sweden
Karolinska University hospital
Stockholm, Sweden
Bristol Brain Centre, Southmead Hospital
Bristol, United Kingdom
Fairfield General Hospital (Pennine Acute NHS Trust)
Bury, United Kingdom
Ninewells Hospital
Dundee, United Kingdom
Lincoln County Hospital
Lincoln, United Kingdom
Charing Cross Hospital, Imperial College Healthcare NHS Trust
London, United Kingdom
The National Hospital of Neurology and Neurosurgery (UCL)
London, United Kingdom
...and 10 more locations
Unified Dyskinesia Rating Scale (UDysRS)
The change from baseline to day 28 of treatment (Visit 4) in the sum of the items comprising the Unified Dyskinesia Rating Scale (UDysRS). The Unified Dyskinesia Rating Scale (UDysRS) is administered to assess dyskinesia. The scoring range is 0-104, where higher score means more dyskinesia.
Time frame: Baseline and 4 weeks
Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV, Question 4.1 and 4.2
Change in MDS-UPDRS sum score of questions 4.1 (Time spent with dyskinesias) and 4.2 (Functional impact of dyskinesias) in part IV from baseline to visit 4. Minimum score is 0 and maximum score is 8. A higher score means more dyskinesia.
Time frame: Baseline and 4 weeks
Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part II and III
Change in MDS-UPDRS sum score of parts II+III (Motor aspects of Experiences of Daily living + Motor Examination) from baseline to visit 4. Minimum value is 0 and maximum value is 124. Higher score mean a worse outcome.
Time frame: Baseline and 4 weeks
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